LSD1 enzyme inhibitor TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models
Rina Baba, Satoru Matsuda, Yuuichi Arakawa, Ryuji Yamada, Noriko Suzuki, Tatsuya Ando, Hideyuki Oki, S. Igaki, Masaki Daini, Yasushi Hattori, Shigemitsu Matsumoto, Mitsuhiro Ito, Atsushi Nakatani, Haruhide Kimura
Abstract
-pyran-4-yl)thiophene-3-carboxamide hydrochloride (TAK-418), almost completely normalized the dysregulated gene expression in the brain and ameliorated some ASD-like behaviors in these models. The genes modulated by TAK-418 were almost completely different across the models and their ages. These results suggest that LSD1 enzyme activity may stabilize the aberrant epigenetic machinery in neurodevelopmental disorders, and the inhibition of LSD1 enzyme activity may be the master key to recover gene expression homeostasis. TAK-418 may benefit patients with neurodevelopmental disorders.